Recent work by others showed that Vitamin C (ascorbic acid) prevented the bronchoconstriction in man resulting from inhalation of histamine aerosol. Further explorations in this laboratory have demonstrated that Vitamin C by itself produced no change in airway muscle tone as judged by specific airway conductance and flow volume curves. But the administration of one gram of ascorbic acid produced a reversal of the constriction within 10 min. after a 30 second inhalation of methacholine aerosol (100 mg/ml). This reversal (dilation) was blocked by ingestion of 50 mg of indomethacin. The object of the present proposal is to examine the dose response relationships and time course of this reversal in people with normal and hyperreactive airways, and to further define the mechanism of action of Vitamin C on the airways and the way in which indomethacin modulates this action. The methods to be used for measurement of airway constriction include the body plethysmograph method for determination of specific airway conductance, and flow volume measurements of partial expiratory flow at 40% vital capacity. The concentration and ratios of different prostaglandins in the blood and urine will be measured in relation to provocative inhalations, and modifications of airway responses by ascorbic acid, indomethacin, and aspirin, in healthy subjects, asthmatics, and bronchitics. From this, the hypothesis that the action of ascorbic acid on human airways is through modulation or prostaglandin synthesis will be tested, and the reason for differences in response to ascorbic acid between healthy humans, asthmatics and bronchitics will be determined.